There is an ongoing effort to develop non-invasive techniques for determining body fluid constituents, such as parameters of living blood. These non-invasive measurement techniques aim to simplify the test and constituents determination procedures, and substantially alleviate the discomfort associated with conventional invasive tests commonly used nowadays.
In case of diabetes, for example, diabetic patients must measure blood glucose by themselves on a daily basis by an ex vivo blood test. Self-monitoring of blood glucose is an important component of modern therapy for diabetic patients and offers information about blood glucose levels, and in many time points to enable stabilization of glucose levels in everyday life. The self-monitoring of blood glucose is suggested to be undertaken at least three or four times a day. However, it is reported that only 18% of diabetic patients periodically measure blood glucose levels, even in good social welfare sectors such as in the USA. Blood glucose measurement negligence is mainly due to invasive-type glucose meters that are used nowadays, that require in each test that blood samples be directly taken from the body of the patient e.g., by piercing a finger of the patient. Such periodical blood tests employing the invasive method not only cause pain and discomfort during the blood taking process, but also impose mental and economic burdens with considerable costs of consumable accessories necessary for the blood taking operation.
Various devices for non-invasive measurement of blood glucose have been developed aiming to prevent the pain and displeasure associated with the conventional blood taking process, to reduce use of diagnostic strips and the costs associated therewith, and to allow smoothly performing self-measurement of blood glucose levels. Such non-invasive blood glucose measurement techniques include, for example, analysis of a absorption spectrum in an infrared zone, impedance spectroscopy in a band of tens to hundreds MHz, and non-invasive blood glucose measurement based on NMR spectroscopy.
Some NMR based blood test techniques known from the patent literature will be briefly discussed below.
U.S. Pat. Nos. 4,875,486, 5,685,300, 6,163,154, 6,404,197 and US patent publication No. 2010/030062A1, disclose NMR based techniques that are basically based on correlation between resonance peaks (or areas) appearing in NMR spectrum of blood (or of tissue) of the human body due to water and glucose components, or on a degree of chemical shift by the glucose component on the measured NMR caused by variations in a blood glucose concentration.
In the publication by Protasov et al., (E. A. Protasov, O. C. Esikov and E. C. Karpova, “Measurement of concentration of glucose in human blood by NMR method,” Scientific session MEPhI Conference, Vol. 5, pp. 3, 2003) a glucose concentration measurement method is described wherein an electromagnetic field is used and blood glucose levels are determined based on correlation between blood glucose levels measured in healthy subjects and a NMR spin-lattice relaxation time measured by a NMR absorption method.
U.S. Pat. No. 7,635,331 discloses a blood glucose sensor using permanent magnets to non-invasively measure blood glucose by means of the NMR absorption method applied to a human finger. In this non-invasive blood glucose sensor, a pair of permanent magnets is used to apply a constant magnetic field so as to remove variations in the magnetic field caused by an unstable power supply. A triangular waveform low frequency modulation magnetic field having uniform strength is used together with a weak acoustic wave modulation magnetic field to determine nuclear spin-lattice relaxation time of the finger's protons from changes of the NMR absorption signal as a function of low frequency modulation sequence. Blood glucose concentration is then determined by correlating between pre-determined blood glucose levels in healthy subjects and the determined proton spin-lattice relaxation time.
International patent publication No. WO 2012/118442 discloses techniques for ex vivo determining infection level of blood cells using magnetic resonance relaxometry. In this publication, a magnetic resonance relaxometry system is used to examine a sample of concentrated red blood cells taken from an examined subject by placing the red blood cells sample within a detection coil of the apparatus and determining an infection level based on transverse relaxation rates.
A non invasive blood fluidity measurement technique is described in EP 2,292,142, which suggests measuring the passage of light in a test site in a finger area of a patient, where pressure is applied over the test site in order to squeeze and flow out blood therefrom to the periphery of the test site.